Glenn J. Hanna, Tulika R. Gupta, Lorenzo Trippa, Eleni M. Rettig, Danielle N. Margalit, Roy B. Tishler, Itai Pashtan, S.E. Kim, Alexander Droznin, Lauren Gunasti, Riley Maddox, J. Minken, Dev Mukundan, Kartik Sehgal, Michael J. Dennis, Thomas O’Connor, Jack M. Qian, Graham Boyd, Anurag Saraf, Daribelle Massiel Gil, Rosh K. Sethi, Donald J. Annino, Lauren A. Goguen, Jeffrey P. Guenette, Mina Bakhtiar, Vickie Y. Jo, Kristine Wong, Ravindra Uppaluri, Robert I. Haddad, Jonathan D. Schoenfeld
Circulating tumor DNA (ctDNA) has an expanding role in oncology. It is unknown whether on-treatment ctDNA can be used to personalize radiation dose. This phase 2 exploratory clinical trial enrolled 102 patients with human papillomavirus (HPV)-positive oropharyngeal carcinoma (OPC). Intermediate-risk patients (T4 disease or >10 pack-year smokers with pre-treatment HPV ctDNA scores >200) were reclassified as low-risk if HPV ctDNA cleared by >95% mid-treatment. All clinically low-risk and reclassified patients received de-intensified (chemo)radiation. The primary outcome was progression-free survival (PFS) among de-escalated patients; secondary outcomes included tolerability, distant metastatic-free, and overall survival. Eighty-nine patients received de-escalated treatment (60 low-risk, 29 reclassified). Two-year PFS among de-escalated patients was 93% (95%CI, 87-99). Post-hoc analyses suggested that intermediate-risk patients reclassified as low-risk and treated with de-escalation had distinct HPV ctDNA dynamics and favorable outcomes. HPV ctDNA is an emerging biomarker that might improve risk stratification for patients with intermediate-risk HPV-positive OPC. Registration number: NCT04900623.